The Ca2+-sensitive K+ channel of human red blood cells (RBCs) (Gardos channel, hIK1, hSK4) was implicated in the progressive densification of RBCs during normal senescence and in the mechanism of sickle cell dehydration. Saturating RBC Ca2+ loads were shown before to induce rapid and homogeneous dehydration, suggesting that Gardos channel capacity was uniform among the RBCs, regardless of age. Using glycated hemoglobin as a reliable RBC age marker, we investigated the age–activity relation of Gardos channels by measuring the mean age of RBC subpopulations exceeding a set high density boundary during dehydration. When K+ permeabilization was induced with valinomycin, the oldest and densest cells, which started nearest to the set density boundary, crossed it first, reflecting conservation of the normal age–density distribution pattern during dehydration. However, when Ca2+ loads were used to induce maximal K+ fluxes via Gardos channels in all RBCs (Fmax), the youngest RBCs passed the boundary first, ahead of the older RBCs, indicating that Gardos channel Fmax was highest in those young RBCs, and that the previously observed appearance of uniform dehydration concealed a substantial degree of age scrambling during the dehydration process. Further analysis of the Gardos channel age–activity relation revealed a monotonic decline in Fmax with cell age, with a broad quasi-Gaussian Fmax distribution among the RBCs.
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1 May 2007
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April 30 2007
Age Decline in the Activity of the Ca2+-sensitive K+ Channel of Human Red Blood Cells
Teresa Tiffert,
Teresa Tiffert
1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
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Nuala Daw,
Nuala Daw
1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
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Zipora Etzion,
Zipora Etzion
2Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
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Robert M. Bookchin,
Robert M. Bookchin
2Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
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Virgilio L. Lew
Virgilio L. Lew
1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
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Teresa Tiffert
1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Nuala Daw
1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Zipora Etzion
2Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
Robert M. Bookchin
2Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
Virgilio L. Lew
1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Correspondence to Teresa Tiffert: [email protected]
Abbreviations used in this paper: DEP, diethylphthalate; Hb A1c, glycated hemoglobin; Hct, hematocrit; RBC, human red blood cell.
Received:
February 14 2007
Accepted:
April 06 2007
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2007
J Gen Physiol (2007) 129 (5): 429–436.
Article history
Received:
February 14 2007
Accepted:
April 06 2007
Citation
Teresa Tiffert, Nuala Daw, Zipora Etzion, Robert M. Bookchin, Virgilio L. Lew; Age Decline in the Activity of the Ca2+-sensitive K+ Channel of Human Red Blood Cells . J Gen Physiol 1 May 2007; 129 (5): 429–436. doi: https://doi.org/10.1085/jgp.200709766
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